Skip to 0 minutes and 21 secondsI'm here with Professor Peter Choong, a colleague from St. Vincent's Hospital in Melbourne, and we'd like to talk to you now about 3D printing and cartilage regeneration. So Peter, I believe there's a real need to develop advanced systems, improved systems, for cartilage regeneration. Absolutely, Gordon. One of the big problems we have in our community is arthritis. About 50% of people over the age of 65 are affected by arthritis in some way. What we do know for a country who are sport-loving and very outdoors, injuries to knees, hips, are quite common. And we believe that it was those initial injuries that may be the thing that started the ball rolling for the development of arthritis.
Skip to 1 minute and 5 secondsThat being the case, if we can isolate the injury and do something about the injury when it first occurred, we may have a chance of treating what could be a very long-term problem for our community. And so how does 3D printing play a role in creating these advanced treatments for cartilage regeneration? Joints are very specialised parts of the body. They have to match. When you have a big pothole in the road, the first thing we know is that anything rolling over that pothole will hit a bump. So we have to smoothen out that pothole.
Skip to 1 minute and 36 secondsAnd what we would like to do is smooth another joint by filling the potholes that may occur in those joints with exactly the sorts of material that cartilage is made for. If we can achieve that, what we are returning to the joint is a smoothness that allows it to function normally, without creating the issues of unevenness or roughness. The bone cartilage interface may be damaged through trauma, removal of tumours, or through diseases such as arthritis. Rebuilding this interface poses a challenge that may now be overcome due to recent advances in micro- and nano-fabrication. Diseased or damaged tissue can be removed using appropriate surgical tools.
Skip to 2 minutes and 19 secondsA 3D scaffold, that fills the defect and provides an environment for cell growth, is then installed. This implant is rather sophisticated. It consists of three layers, with a composition and structure appropriate to encourage bone re-growth, cartilage regeneration, and the effective integration of both. In the bottom layer, immediately adjacent to the bone, seeding with osteoblast cells assists with bone regeneration. Seeding other layers in the scaffold with osteochondral cells and chondrocytes then enables production of extracellular matrix molecules, such as collagen, that are needed to rebuild cartilage. Cells continue to fill the scaffold, producing extracellular molecules, ensuring reconstruction of cartilage and the bound cartilage interface. We will utilise electrical stimulation of nanostructured electrodes strategically positioned within the scaffold to facilitate the regeneration process.
Skip to 3 minutes and 18 secondsThe ideal outcome is complete repair of the damage site with functional cartilage. In this application, control over the spatial distribution of composition and structure in three dimensions is critical. And as I understand it, the patient's own stem cells may play a role in this regeneration process, with the 3D printed structure. Absolutely. If we can get cells that match the patients as closely as possible, then you don't have the problem of rejection. What we're trying to do, and what we've actually succeeded in our laboratories, is isolating certain cells from the patient and helping these cells move down the pathway to developing the patient's own cartilage.
Skip to 4 minutes and 0 secondsSo structures that you can 3D print, that we then populate with the patient's own stem cells, become the types of structures that we can implant into these defects of cartilage.
Skip to 4 minutes and 16 secondsSo now, I guess the questions around design really take on different aspects. Because we're talking about where we might put the structural polymer that supports the cartilage regeneration, but where we might also distribute those stem cells or other bioactives throughout that 3D structure to get optimal performance. Absolutely. Although cartilage seems like a very simple structure, a very thin structure, in fact, it's quite complex. It's made of a microstructure of collagen that is arranged in very specific ways to undertake the stress of compression, of shear, as well as being able to contain the fluids that give it its compressive strength. Now, holding it all together is a matrix that cartilage cells produce.
Skip to 5 minutes and 6 secondsWhere we place these cartilage cells become quite important, in terms of how we create a structure that functions like cartilage. So this ability to distribute things in three dimensions-- whether that's mechanical properties or biological activity-- I mean, this is something that we just couldn't do before the advent of 3D printing, correct? Absolutely. Knowing how to print, the ability to lay the collagen microstructure, were all extremely difficult to achieve. Not only have we overcome that, by the ability to electrospin or 3D print, we can actually print cells at the same time. The bio-ink that we use for example, contains the cells that are required to populate the structure.
Skip to 5 minutes and 55 secondsSo we've resolved many, many questions by the progress of science in this area. So Peter has mentioned to you the need to deliver both the structural support and the stem cells together during the printing process, as we continue to develop this technology. To do that, we have developed together a BioPen-- a handheld 3D printer. I'll let Peter explain how that works. So Gordon, as a surgeon, we are in surgery with the patient's part open to us. And what we would like to do is actually sculpt out an area to fill the defect in the cartilage, for example.
Skip to 6 minutes and 32 secondsThe BioPen is such a perfect instrument for this, because held in the surgeon's own hand is a device that not only delivers the ink that fills the defect, it has another tube running right next to it that also delivers the cell. Being able to use this real time means we can be as patient-specific as we can, in order to repair the defect in the cartilage. And so these advances in the ink, and the understanding of the stem cell behaviour, and the ability to deliver it. And what impact will it have on cartilage regeneration, say in the next five years? It may well change the entire paradigm of how we treat early injury to cartilage, and its impact on arthritis.
Skip to 7 minutes and 14 secondsSo this is an excellent example that shows that the clinical need needs to draw on advances in materials and biology, but also engineering, in order to provide the clinical solution. Absolutely. This multi-disciplinary approach is what's going to make it possible for physicians and surgeons like me to deal with diseases today and to engineer solutions for these diseases.
Case study: Cartilage part 1
Of all of the tissues under investigation for replacement via tissue engineering, cartilage is at the forefront.
Of particular importance for knee ‘engineering’ is the articular cartilage, the stretchy cartilage that coats the surface of bones in working joints such as the knee. There are a few reasons for this:
Cartilage is non-vascular. That is, it does not have dense capillaries distributed through it like many other tissues.
There are very few resident stem cells available within articular hyaline cartilage. This means that there is little chance of cartilage regeneration. It is as though the body never anticipated needing to regenerate this critical element in joints.
There is not only a huge need (consider athlete sporting injuries alone, not to mention those affected by osteoarthritis) for this kind of critical cartilage repair, but the alternatives at this stage are archaic in nature. While many treatments have been proposed and attempted, the go-to procedure for surgeons is still the ‘microfracture’ process, in which the underlying bone is drilled repeatedly to release a ‘super-clot’ of blood infused with stem cells from the marrow, to assist in the cartilage formation.
As you saw in the video, Professor Wallace and Dr Choong have developed a biopen that could provide a clinical solution for cartilage regeneration. Read about the development of the biopen in the next step.
© University of Wollongong, 3D Bioprinting: Printing parts for bodies, 2014, Wallace, G.G., Cornock, R.C., O’Connell, C.D., Beirne, S., Dodds, S., Gilbert, F.